Economic Burden of Eosinophilic Esophagitis: A Nationwide Cost-of-Illness Study.

INTRODUCTION: Despite its increasing prevalence, the economic impact of eosinophilic esophagitis (EoE) is understudied. METHODS: We estimated the societal economic burden of EoE by using real-world data from Swedish health registers. RESULTS: Patients with EoE had 45% higher societal cost ($6,290 vs $4,349) compared with the general population, primarily driven by increased healthcare costs ($2,414 vs $1,022), which accounted for 72% of the excess societal cost in EoE. DISCUSSION: EoE is associated with a considerable economic burden to society. With the prevalence of EoE still rising, the economic burden of EoE is expected to continue to grow.

Real-World Healthcare Cost Savings and Reduced Relapse Rate with Off-Label Rituximab versus Disease-Modifying Treatments Approved for Relapsing-Remitting Multiple Sclerosis: A Nationwide Cost-Effectiveness Study.

OBJECTIVE: Although off-label use of rituximab is a common alternative to disease-modifying therapies (DMTs) approved for multiple sclerosis (MS) in several countries, the impact of this on treatment cost-effectiveness is not well known. METHODS: We evaluated the relative cost-effectiveness of rituximab and MS-approved DMTs in a register-based cohort study of Swedish residents with relapsing-remitting MS, aged 18-65 years, starting treatment with rituximab, natalizumab, fingolimod, or dimethyl fumarate between January 2010 and July 2016, and followed through July 2021 (n = 5,924). By linking the population-based Swedish MS register to several Swedish health care and demographic registers, we estimated health care costs in relation to number of relapses, over 5 years from treatment start. Differences between treatments were estimated in inverse probability of treatment-weighted regression models, adjusting for a broad range of potential confounders covering demographics, medical history, and MS-related clinical characteristics. RESULTS: Off-label rituximab was associated with both lower total health care costs (mean cost savings ranged $35,000-$66,000 vs. each approved DMT), and fewer relapses (mean number of prevented relapses ranged 0.12-0.22), per started therapy over 5 years. Results were robust to variations in discounting and pricing of health care visits, with the main driver of cost-savings being the price of the index drug itself. INTERPRETATION: The cost-effectiveness of rituximab dominated the MS-approved alternatives. Off-label, low-dose rituximab should be considered for persons with MS and could reduce barriers to treatment, especially in resource-limited settings. ANN NEUROL 2024;95:1099-1111.

Increasing healthcare costs in inflammatory bowel disease 2007-2020 in Sweden.

BACKGROUND: Inflammatory bowel disease has been linked to increasing healthcare costs, but longitudinal data on other societal costs are scarce. AIM: To assess costs, including productivity losses, in patients with prevalent Crohn's disease (CD) or ulcerative colitis (UC) in Sweden between 2007 and 2020. METHODS: We linked data from national registers on all patients with CD or UC and a matched (sex, birthyear, healthcare region and education) reference population. We assessed mean costs/year in Euros, inflation-adjusted to 2020, for hospitalisations, out-patient visits, medications, sick leave and disability pension. We defined excess costs as the mean difference between patients and matched comparators. RESULTS: Between 2007 and 2020, absolute mean annual societal costs in working-age (18-64 years) individuals decreased by 17% in CD (-24% in the comparators) and by 20% in UC (-27% in comparators), due to decreasing costs from sick leave and disability, a consequence of stricter sick leave regulations. Excess costs in 2007 were dominated by productivity losses. In 2020, excess costs were mostly healthcare costs. Absolute and excess costs increased in paediatric and elderly patients. Overall, costs for TNF inhibitors/targeted therapies increased by 274% in CD and 638% in UC, and the proportion treated increased from 5% to 26% in CD, and from 1% to 10% in UC. CONCLUSION: Between 2007 and 2020, excess costs shifted from productivity losses to direct healthcare costs; that is, the patients' compensation for sickness absence decreased, while society increased its spending on medications. Medication costs were driven both by expanding use of TNF inhibitors and by high costs for newer targeted therapies.

Healthcare use, work loss and total costs in incident and prevalent Crohn's disease and ulcerative colitis: results from a nationwide study in Sweden.

BACKGROUND: There are limited data on population-wide assessment of cost in Crohn's disease (CD) and ulcerative colitis (UC). AIM: To estimate the societal cost of actively treated CD and UC in Sweden. METHODS: We identified 10 117 prevalent CD and 19 762 prevalent UC patients, aged ≥18 years on 1 January 2014 and 4028 adult incident CD cases and 8659 adult incident UC cases (2010-2013) from Swedish Patient Register. Each case was matched to five population comparators. Healthcare costs were calculated from medications, outpatient visits, hospitalisations and surgery. Cost of productivity losses was derived from disability pension and sick leave. RESULTS: The mean annual societal costs per working-age patient (18-64 years) with CD and UC were $22 813 (vs $7533 per comparator) and $14 136 (vs $7351 per comparator), respectively. In patients aged ≥65 years, the mean annual costs of CD and UC were $9726 and $8072 vs $3875 and $4016 per comparator, respectively. The majority of cost for both CD (56%) and UC (59%) patients originated from productivity losses. Higher societal cost of working-age CD patients as compared to UC patients was related to greater utilisation of anti-TNF (22.2% vs 7.4%) and increased annual disability pension (44 days vs 25 days). Among incident CD and UC patients, the mean total cost over the first year per patient was over three times higher than comparators. CONCLUSION: In Sweden, the societal cost of incident and prevalent CD and UC patients was consistently two to three times higher than the general population.

Costs and Use of Health Care in Patients With Celiac Disease: A Population-Based Longitudinal Study.

INTRODUCTION: Celiac disease (CD) affects 1% of the population. Its effect on healthcare cost, however, is barely understood. We estimated healthcare use and cost in CD, including their temporal relationship to diagnosis. METHODS: Through biopsy reports from Sweden's 28 pathology departments, we identified 40,951 prevalent patients with CD (villous atrophy) as of January 1, 2015, and 15,086 incident patients with CD diagnosed in 2008-2015, including 2,663 who underwent a follow-up biopsy to document mucosal healing. Each patient was compared with age- and sex-matched general population comparators (n = 187,542). Using nationwide health registers, we retrieved data on all inpatient and nonprimary outpatient care, prescribed diets, and drugs. RESULTS: Compared with comparators, healthcare costs in 2015 were, on average, $1,075 (95% confidence interval, $864-1,278) higher in prevalent patients with CD aged <18 years, $715 ($632-803) in ages 18-64 years, and $1,010 ($799-1,230) in ages ≥65 years. Half of all costs were attributed to 5% of the prevalent patients. Annual healthcare costs were $391 higher 5 years before diagnosis and increased until 1 year after diagnosis; costs then declined but remained 75% higher than those of comparators 5 years postdiagnosis (annual difference = $1,044). Although hospitalizations, nonprimary outpatient visits, and medication use were all more common with CD, excess costs were largely unrelated to the prescription of gluten-free staples and follow-up visits for CD. Mucosal healing in CD did not reduce the healthcare costs. DISCUSSION: The use and costs of health care are increased in CD, not only before, but for years after diagnosis. Mucosal healing does not seem to lower the healthcare costs.

The longitudinal integrated database for health insurance and labour market studies (LISA) and its use in medical research.

Education, income, and occupation are factors known to affect health and disease. In this review we describe the Swedish Longitudinal Integrated Database for Health Insurance and Labour Market Studies (LISA, Longitudinell Integrationsdatabas för Sjukförsäkrings- och Arbetsmarknadsstudier). LISA covers the adult Swedish population aged ≥ 16 years registered on December 31 each year since 1990 (since 2010 individuals aged ≥ 15 years). The database was launched in response to rising levels of sick leave in the country. Participation in Swedish government-administered registers such as LISA is compulsory, and hence selection bias is minimized. The LISA database allows researchers to identify individuals who do not work because of injury, disease, or rehabilitation. It contains data on sick leave and disability pension based on calendar year. LISA also includes information on unemployment benefits, disposable income, social welfare payments, civil status, and migration. During 2000-2017, an average of 97,000 individuals immigrated to Sweden each year. This corresponds to about 1% of the Swedish population (10 million people in 2017). Data on occupation have a completeness of 95%. Income data consist primarily of income from employment, capital, and allowances, including parental allowance. In Sweden, work force participation is around 80% (2017: overall: 79.1%; men 80.3% and women 77.9%). Education data are available in > 98% of all individuals aged 25-64 years, with an estimated accuracy for highest attained level of education of 85%. Some information on civil status, income, education, and employment before 1990 can be obtained through the Population and Housing Census data (FoB, Folk- och bostadsräkningen).

Sick Leave and Disability Pension in Prevalent Patients With Crohn's Disease.

BACKGROUND AND AIMS: Crohn's disease may affect the ability to work and lead to permanent disability. We aimed to investigate work loss in prevalent patients. METHODS: We identified patients with Crohn's disease and general population comparators matched by sex, birth year, healthcare region and education. We assessed days of sick leave and disability pension retrieved from the Swedish Social Insurance Agency and estimated the absolute and relative risk of receiving disability pension [minimum 25% work impairment]. RESULTS: In 2014, the 20638 Crohn's disease patients [median age 44 years] had more than twice as many mean lost workdays [disability pension: 44; sick leave: 19] as the 102038 comparators [disability pension: 20; sick leave: 8], mean difference 35 days [95% confidence interval 33-37]. However, the majority had no lost workdays [68% of patients and 85% of comparators]. The proportion of patients receiving disability pension was 15% (6.5% in the comparators, risk ratio 2.34 [2.25-2.43]) and was higher in all subgroups, especially in female patients [28% vs 13% in the comparators], in those with ≤9 years of education [41% vs 23%] and in ages 60-64 years [46% vs 25%]. The relative risk of disability pension within the patient cohort [adjusted for age, sex, region and education] was higher in patients with complicated disease behaviour, extraintestinal manifestations, need of surgery or treatment with biologics. The differences between patients and comparators remained when comparing other calendar years [2006-2013]. CONCLUSION: Work loss was found in approximately one-third of patients. The mean number of lost workdays was twice as high as in the comparators.

Healthcare costs in chronic kidney disease and renal replacement therapy: a population-based cohort study in Sweden.

OBJECTIVE: To compare healthcare costs in chronic kidney disease (CKD) stage 4 or 5 not on dialysis (estimated glomerular filtration rate <30 mL/min/1.73m2), peritoneal dialysis, haemodialysis and in transplanted patients with matched general population comparators. DESIGN: Population-based cohort study. SETTING: Swedish national healthcare system. PARTICIPANTS: Prevalent adult patients with CKD 4 or 5 (n=1046, mean age 68 years), on peritoneal dialysis (n=101; 64 years), on haemodialysis (n=460; 65 years) and with renal transplants (n=825; 52 years) were identified in Stockholm County clinical quality registers for renal disease on 1 January 2010. 5 general population comparators from the same county were matched to each patient by age, sex and index year. PRIMARY AND SECONDARY OUTCOME MEASURES: Annual healthcare costs in 2009 incurred through inpatient and hospital-based outpatient care and dispensed prescription drugs ascertained from nationwide healthcare registers. Secondary outcomes were annual number of hospital days and outpatient care visits. RESULTS: Patients on haemodialysis had the highest mean annual cost (€87 600), which was 1.49 (95% CI 1.38 to 1.60) times that observed in peritoneal dialysis (€58 600). The mean annual cost was considerably lower in transplanted patients (€15 500) and in the CKD group (€9600). In patients on haemodialysis, outpatient care costs made up more than two-thirds (€62 500) of the total, while costs related to fluids ($29 900) was the largest cost component in patients on peritoneal dialysis (51%). Compared with their matched general population comparators, the mean annual cost (95% CI) in patients on haemodialysis, peritoneal dialysis, transplanted patients and patients with CKD was 45 (39 to 51), 29 (22 to 37), 11 (10 to 13) and 4.0 (3.6 to 4.5) times higher, respectively. CONCLUSIONS: The mean annual costs were ∼50% higher in patients on haemodialysis than in those on peritoneal dialysis. Compared with the general population, costs were substantially elevated in all groups, from 4-fold in patients with CKD to 11, 29 and 45 times higher in transplanted patients and patients on peritoneal dialysis and haemodialysis, respectively.

Costs in Relation to Disability, Disease Activity, and Health-related Quality of Life in Rheumatoid Arthritis: Observational Data from Southern Sweden.

OBJECTIVE: To compare how costs relate to disability, disease activity, and health-related quality of life (HRQOL) in rheumatoid arthritis (RA). METHODS: Antitumor necrosis factor (anti-TNF)-treated patients with RA in southern Sweden (n = 2341) were monitored 2005-2010. Health Assessment Questionnaire (HAQ), 28-joint Disease Activity Score (DAS28), and EQ-5D scores were linked to register-derived costs of antirheumatic drugs (excluding anti-TNF agents), patient care, and work loss from 30 days before to 30 days after each visit (n = 13,289). Associations of HAQ/DAS28/EQ-5D to healthcare (patient care and drugs) and work loss costs (patients < 65 yrs) were studied in separate regression models, comparing standardized ß coefficients by nonparametric bootstrapping to assess which measure best reflects costs. Analyses were conducted based on both individual means (linear regression, comparing between-patient associations) and by generalized estimating equations (GEE), using all observations to also account for within-patient associations of HAQ/DAS28/EQ-5D to costs. RESULTS: Regardless of the methodology (linear or GEE regression), HAQ was most closely related to both cost types, while work loss costs were also more closely associated with EQ-5D than DAS28. The results of the linear models for healthcare costs were standardized ß = 0.21 (95% CI 0.15-0.27), 0.16 (0.11-0.21), and -0.15 (-0.21 to -0.10) for HAQ/DAS28/EQ-5D, respectively (p < 0.05 for HAQ vs DAS28/EQ-5D). For work loss costs, the results were standardized ß = 0.43 (95% CI 0.39-0.48), 0.27 (0.23-0.32), and -0.34 (-0.38 to -0.29) for HAQ/DAS28/EQ-5D, respectively (p < 0.05 for HAQ vs DAS28/EQ-5D and for EQ-5D vs DAS28). CONCLUSION: Overall, HAQ disability is a better marker of RA costs than DAS28 or EQ-5D HRQOL.

Registers of the Swedish total population and their use in medical research.

The primary aim of the Swedish national population registration system is to obtain data that (1) reflect the composition, relationship and identities of the Swedish population and (2) can be used as the basis for correct decisions and measures by government and other regulatory authorities. For this purpose, Sweden has established two population registers: (1) The Population Register, maintained by the Swedish National Tax Agency ("Folkbokföringsregistret"); and (2) The Total Population Register (TPR) maintained by the government agency Statistics Sweden ("Registret över totalbefolkningen"). The registers contain data on life events including birth, death, name change, marital status, family relationships and migration within Sweden as well as to and from other countries. Updates are transmitted daily from the Tax Agency to the TPR. In this paper we describe the two population registers and analyse their strengths and weaknesses. Virtually 100 % of births and deaths, 95 % of immigrations and 91 % of emigrations are reported to the Population Registers within 30 days and with a higher proportion over time. The over-coverage of the TPR, which is primarily due to underreported emigration data, has been estimated at up to 0.5 % of the Swedish population. Through the personal identity number, assigned to all residents staying at least 1 year in Sweden, data from the TPR can be used for medical research purposes, including family design studies since each individual can be linked to his or her parents, siblings and offspring. The TPR also allows for identification of general population controls, participants in cohort studies, as well as calculation of follow-up time.

Does disease activity at start of biologic therapy influence work-loss in RA patients?

OBJECTIVE: To compare work-loss in RA patients starting their first biologic with high vs moderate disease activity. METHODS: We identified all RA patients aged 20-63 years in the Swedish Biologics Register who started their first biologic 2007-09 with high disease activity (DAS28 >5.1; n = 868) or moderate disease activity (DAS28 3.2-5.1; n = 854). Work days lost, defined as sick leave and disability pension days from the Swedish Social Insurance Agency, were assessed over 5 years after first bio-start. We estimated between-group mean differences adjusted for age, sex, calendar year, education level, disease duration, comorbidities and work-loss the month before bio-start. RESULTS: During 5 years after anti-TNF start, mean monthly work days lost declined from 16.0 to 9.2 (42%; P < 0.001) in patients with high disease activity at baseline and from 12.0 to 7.2 (40%; P < 0.001) in patients with moderate disease activity, with no between-group difference (adjusted mean difference 0.81; 95% CI - 0.44, 2.05). Accumulated 5-year work-loss was, however, higher in the high activity group (724 vs 548 days; adjusted mean difference 70; 95% CI 20, 120), but after stratification on baseline disability pension status, no differences in accumulated work-loss were detected. CONCLUSION: Substantial work-loss was seen in both patients with high and patients with moderate disease activity at anti-TNF start, with a 5-year decline in mean monthly work days lost by ∼40% in both groups and no between-group difference. Accumulated work-loss over 5 years was higher in the high-activity group, which may be explained by differences in baseline disability pension status.

Health-care costs over 15 years after bariatric surgery for patients with different baseline glucose status: results from the Swedish Obese Subjects study.

BACKGROUND: Bariatric surgery prevents and induces remission of type 2 diabetes in many patients. The effect of preoperative glucose status on long-term health-care costs is unknown. We aimed to assess health-care costs over 15 years for patients with obesity treated conventionally or with bariatric surgery and who had either euglycaemia, prediabetes, or type 2 diabetes before intervention. METHODS: The Swedish Obese Subjects (SOS) study is a prospective study of adults who had bariatric surgery and contemporaneously matched controls who were treated conventionally (age 37-60 years; BMI of ≥34 in men and ≥38 in women) recruited from 25 Swedish surgical departments and 480 primary health-care centres. Exclusion criteria were identical for both study groups, and were previous gastric or bariatric surgery, recent malignancy or myocardial infarction, selected psychiatric disorders, and other contraindicating disorders to bariatric surgery. Conventional treatment ranged from no treatment to lifestyle intervention and behaviour modification. In this study, we retrieved prescription drug costs for the patients in the SOS study via questionnaires and the nationwide Swedish Prescribed Drug Register. We retrieved data for inpatient and outpatient visits from the Swedish National Patient Register. We followed up the sample linked to register data for up to 15 years. We adjusted mean differences for baseline characteristics. Analyses were by intention to treat. The SOS study is registered with ClinicalTrials.gov, number NCT01479452. FINDINGS: Between Sept 1, 1987, and Jan 31, 2001, 2010 adults who had bariatric surgery and 2037 who were treated conventionally were enrolled into the SOS study. In this study, we followed up 4030 patients (2836 who were euglycaemic; 591 who had prediabetes; 603 who had diabetes). Drug costs did not differ between the surgery and conventional treatment groups in the euglycaemic subgroup (surgery US$10,511 vs conventional treatment $10,680; adjusted mean difference -$225 [95% CI -2080 to 1631]; p=0·812), but were lower in the surgery group in the prediabetes ($10,194 vs $13,186; -$3329 [-5722 to -937]; p=0·007) and diabetes ($14,346 vs $19,511; -$5487 [-7925 to -3049]; p<0·0001) subgroups than in the conventional treatment group. Compared with the conventional treatment group, we noted greater inpatient costs in the surgery group for the euglycaemic ($51,225 vs $25,313; $22,931 [19,001-26,861]; p<0·0001), prediabetes ($58,699 vs $32,861; $27,152 [18,736-35,568]; p<0·0001), and diabetes ($61,569 vs $47,569; 18,697 [9992-27,402]; p<0·0001) subgroups. We noted no differences in outpatient costs. Total health-care costs were higher in the surgery group in the euglycaemic ($71,059 vs $45,542; $22,390 [17,358-27,423]; p<0·0001) and prediabetes ($78,151 vs $54,864; $26,292 [16,738-35,845]; p<0·0001) subgroups than in the conventional treatment group, whereas we detected no difference between treatment groups in patients with diabetes ($88,572 vs $79,967; $9081 [-1419 to 19,581]; p=0·090). INTERPRETATION: Total health-care costs were higher for patients with euglycaemia or prediabetes in the surgery group than in the conventional treatment group, but we detected no difference between the surgery and conventional treatment groups for patients with diabetes. Long-term health-care cost results support prioritisation of patients with obesity and type 2 diabetes for bariatric surgery. FUNDING: AFA Försäkring and Swedish Scientific Research Council.

Does disease activity at the start of biologic therapy influence health care costs in patients with RA?

OBJECTIVE: To investigate whether disease activity at baseline influences health care costs in patients with RA initiating biologic treatment. METHODS: In the Swedish Biologics Register, we identified patients with RA with baseline 28-joint DAS (DAS28) recorded and starting their first biologic in 2007-11 [n = 1638 with moderate disease activity (DAS28 3.2-5.1) and n = 1870 with high disease activity (DAS28 > 5.1)]. Data on inpatient and outpatient care and prescription drugs were retrieved from nationwide registers. Mean cost differences were estimated adjusted for age, sex and costs the year before treatment start. RESULTS: Patients with high (vs moderate) disease activity were older (60 vs 56 years; P < 0.001), but did not differ in sex distribution (75 vs 74% women; P = 0.99) or disease duration (10 vs 10 years; P = 0.13). The year after initiation of biologics, patients with high (vs moderate) baseline disease activity accumulated 9% higher health care costs, but the difference was not statistically significant after adjustment [€19,333 vs €17,810; adjusted difference €870 (95% CI -2, 1742)]. In the subgroup of patients with up to 4 years of follow-up data, decreasing costs were observed over the follow-up time, but no difference was found between patients with high compared with moderate baseline disease activity [€13,704 vs €12,349; adjusted difference 878 (95% CI -364, 2120)]. Irrespective of baseline disease activity, health care costs were approximately three times higher the year after initiation of biologics than the year before due to increased drug costs. CONCLUSION: Over up to 4 years of follow-up, no difference in health care costs was found after adjustment in patients starting their first biologic treatment with high vs moderate baseline disease activity.

Costs for hospital care, drugs and lost work days in incident and prevalent rheumatoid arthritis: how large, and how are they distributed?

OBJECTIVE: To estimate the costs related to hospital care, drug use and work loss in prevalent and incident patients with rheumatoid arthritis (RA), and to describe their distribution. METHODS: A cohort of prevalent patients with RA ≥18 years on Jan 1, 2010, was identified from the Swedish National Patient Register (requiring ≥2 visits listing RA) and the Swedish Rheumatology Quality Register, and followed until 31 December 2010. From the same registers, patients with the 1st visit listing RA in 2009, with a 2nd visit within 1 year, were identified to the incident cohort, and were followed for 1 year. Five sex-matched, age-matched, education-matched and county-matched general population comparators were sampled per patient with RA. Costs were retrieved from national registers. RESULTS: The mean annual cost, including productivity losses per patients with RA (n=49 829) aged 18-64 years was €23 147 versus €8364 (median €15 059 vs €277) per comparator. In patients with RA ≥65 years, the mean healthcare cost was €6438 versus €2773 (median €2458 vs €677) per comparator. 13% of the patients accounted for 50% of the cost. For the incident patients with RA (n=2695), the mean monthly cost increased from a level close to the comparators 1 year before register identification (18-64 years: €736 vs €644; ≥65 years: €192 vs €178), peaked the month following the identification date, and decreased to twice the cost of the comparators 1 year after diagnosis (18-64 years: €1252 vs €628; ≥65 years: €487 vs €230). CONCLUSIONS: The mean annual cost in patients with established RA, and mean monthly cost in newly diagnosed patients with RA, were 2-3 times higher than in the general population.

Cost-effectiveness of infliximab versus conventional combination treatment in methotrexate-refractory early rheumatoid arthritis: 2-year results of the register-enriched randomised controlled SWEFOT trial.

OBJECTIVE: To estimate the incremental cost-effectiveness of infliximab versus conventional combination treatment over 21 months in patients with methotrexate-refractory early rheumatoid arthritis. METHODS: In this multicentre, two-arm, parallel, randomised, active-controlled, open-label trial, rheumatoid arthritis patients with <1 year symptom duration were recruited from 15 rheumatology clinics in Sweden between October 2002 and December 2005. After 3-4 months of methotrexate monotherapy, patients not achieving low disease activity were randomised to addition of infliximab or sulfasalazine+hydroxychloroquine (conventional treatment group). Costs of drugs, healthcare use, and productivity losses were retrieved from nationwide registers, while EuroQol 5-Dimensions utility was collected quarterly. RESULTS: Of 487 patients initially enrolled, 128 and 130 were randomised to infliximab and conventional treatment, respectively. The infliximab group accumulated higher drug and healthcare costs (€27,487 vs €10,364; adjusted mean difference €16,956 (95% CI 14,647 to 19,162)), while productivity losses did not differ (€33,804 vs €29,220; €3961 (95% CI -3986 to 11,850)), resulting in higher societal cost compared to the conventional group (€61,291 vs €39,584; €20,916 (95% CI 12,800 to 28,660)). Mean accumulated quality-adjusted life-years (QALYs) did not differ (1.10 vs 1.12; adjusted mean difference favouring infliximab treatment 0.01 (95% CI -0.07 to 0.08)). The incremental cost-effectiveness ratios for the infliximab versus conventional treatment strategy were €2,404,197/QALY from the societal perspective and €1,948,919/QALY from the healthcare perspective. CONCLUSIONS: In early, methotrexate-refractory rheumatoid arthritis, a treatment strategy commencing with addition of infliximab, as compared to sulfasalazine+hydroxychloroquine, was not cost-effective over 21 months at willingness to pay levels generally considered acceptable. TRIAL REGISTRATION NUMBER: NCT00764725.

4-Year Cost Trajectories in Real-World Patients Matched to the Metabolic Profiles of Trial Subjects Before/After Treatment with Phentermine-Topiramate.

OBJECTIVE: Our objective was to estimate 4-year healthcare costs associated with the metabolic profile of patients before and after 1 year of treatment with phentermine (15 mg) and topiramate extended-release (92 mg) [phentermine-topiramate ER]. DESIGN AND METHODS: Using a medical records database, we created two patient cohorts reflecting metabolic profiles of subjects before and after phentermine-topiramate ER therapy during the 1-year CONQUER trial. We matched database patients with trial subjects by age, sex, body mass index (BMI), and hypertension, glycemic, and triglyceride status. We collected real-world data on emergency department and outpatient visits, hospitalizations, and drug prescriptions over 4 years, linking them to reimbursements to estimate US private insurance costs for post-trial (n = 2295) versus pre-trial intention-to-treat (ITT) patients (n = 2295). Secondary analysis assessed responders (completers losing ≥5 % body weight [n = 1285]). RESULTS: Over 4 years, the mean cost per patient in the post- versus pre-trial ITT-group was $US32,432 versus $US34,725 (mean difference -2292; 95 % confidence interval [CI] -4776 to 209). In responders, corresponding costs were $US30,558 versus $US33,936 (mean difference -3378; 95 % CI -6496 to -464). Costs for post- versus pre-trial responders were lower for outpatient visits, emergency visits, and medications (all P < 0.05). CONCLUSION: Excluding treatment cost and potential side effects, patients matched to profiles of phentermine-topiramate ER responders had lower costs than patients matched to pre-treatment profiles.

Biological vs. conventional combination treatment and work loss in early rheumatoid arthritis: a randomized trial.

IMPORTANCE: The introduction of biological tumor necrosis factor inhibitors has improved the treatment of rheumatoid arthritis (RA) but at a substantial cost. These drugs have been shown to lead to superior radiological outcomes compared with a combination of conventional disease-modifying antirheumatic drugs over 2 years. OBJECTIVE: To investigate whether radiological superiority translates into better work loss outcomes. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, 2-arm, parallel, randomized, active-controlled, open-label trial. Patients with early RA (symptom duration <1 year) were recruited from 15 rheumatology clinics in Sweden from October 1, 2002, through December 31, 2005. The study population was restricted to working-age patients (aged <63 years). INTERVENTIONS: Patients who did not achieve low disease activity after 3 to 4 months of methotrexate therapy were randomized to receive additional biological treatment with infliximab or conventional combination treatment with sulfasalazine plus hydroxychloroquine. MAIN OUTCOMES AND MEASURES: Monthly sick leave and disability pension days 21 months after randomization retrieved from the nationwide Swedish Social Insurance Office register. Main analyses were by intention to treat, including all patients, and adjusted for baseline sick leave and disability pension. RESULTS: Of 204 eligible patients, 105 were randomized to biological and 99 to conventional treatment. Seven patients in the biological and 4 in the conventional treatment group never received the study drug, and 72 and 52 patients, respectively, followed the study per protocol for 21 months. The baseline mean (SD) work loss was 17 (13) d/mo (median, 16 d/mo) in both groups (mean difference, 0.6 d/mo; 95% CI, -3.0 to 3.9). The mean changes in work loss at 21 months were -4.9 d/mo in the biological and -6.2 d/mo in the conventional treatment group (adjusted mean difference, 1.6 d/mo; 95% CI, -1.2 to 4.4). Including only patients receiving at least 1 dose of assigned treatment, the adjusted mean difference was 1.5 d/mo (95% CI, -1.5 to 4.4), and in per-protocol analysis the adjusted mean difference was 0.3 d/mo (95% CI, -2.8 to 3.8). CONCLUSIONS AND RELEVANCE: The radiological superiority of biological compared with conventional combination therapy did not translate into better work loss outcomes in patients with early RA who had experienced an insufficient response to methotrexate. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00764725.

Incidence of rheumatoid arthritis in Sweden: a nationwide population-based assessment of incidence, its determinants, and treatment penetration.

OBJECTIVE: To estimate the nationwide incidence of rheumatoid arthritis (RA) in Sweden, including its variation across age, sex, geography, and demography, and to describe the sensitivity of register-based incidence estimates to different RA case definitions. METHODS: Incident RA patients were identified using the Swedish National Patient Register. In the base case, incident RA was defined as first-ever inpatient or nonprimary outpatient care visit listing an RA diagnosis in 2006-2008, with a second visit listing RA within 1 year. Patients prescribed disease-modifying antirheumatic drugs more than 6 months prior to the first visit listing RA were not regarded as incident. The robustness of this definition was evaluated by more liberal and strict criteria, and by penetration of antirheumatic treatment. RESULTS: Between 2006 and 2008, 8,826 individuals were identified as incident RA patients. The overall incidence was 41 per 100,000 (56 for women, 25 for men). The incidence increased with age and peaked in the 70-79 years age group for both women and men. The age- and sex-standardized incidences were lower in densely populated areas and in individuals with high educational level. No geographic trends were noted. More liberal and strict definitions of RA only altered the observed incidence by approximately 14%. CONCLUSION: The overall nationwide register-based incidence of RA was robust across different case definitions. In a country with universal access to care, RA displayed demographic and socioeconomic, but no geographic, variations in incidence, and peaks at an older age than most commonly reported, with no difference in peak age at RA onset between sexes.

Health care use during 20 years following bariatric surgery.

CONTEXT: Bariatric surgery results in sustained weight loss; reduced incidence of diabetes, cardiovascular events, and cancer; and improved survival. The long-term effect on health care use is unknown. OBJECTIVE: To assess health care use over 20 years by obese patients treated conventionally or with bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS: The Swedish Obese Subjects study is an ongoing, prospective, nonrandomized, controlled intervention study conducted in the Swedish health care system that included 2010 adults who underwent bariatric surgery and 2037 contemporaneously matched controls recruited between 1987 and 2001. Inclusion criteria were age 37 years to 60 years and body mass index of 34 or higher in men and 38 or higher in women. Exclusion criteria were identical in both groups. INTERVENTIONS: Of the surgery patients, 13% underwent gastric bypass, 19% gastric banding, and 68% vertical-banded gastroplasty. Controls received conventional obesity treatment. MAIN OUTCOME MEASURES: Annual hospital days (follow-up years 1 to 20; data capture 1987-2009; median follow-up 15 years) and nonprimary care outpatient visits (years 2-20; data capture 2001-2009; median follow-up 9 years) were retrieved from the National Patient Register, and drug costs from the Prescribed Drug Register (years 7-20; data capture 2005-2011; median follow-up 6 years). Registry linkage was complete for more than 99% of patients (4044 of 4047). Mean differences were adjusted for baseline age, sex, smoking, diabetes status, body mass index, inclusion period, and (for the inpatient care analysis) hospital days the year before the index date. RESULTS: In the 20 years following their bariatric procedure, surgery patients used a total of 54 mean cumulative hospital days compared with 40 used by those in the control group (adjusted difference, 15; 95% CI, 2-27; P = .03). During the years 2 through 6, surgery patients had an accumulated annual mean of 1.7 hospital days vs 1.2 days among control patients (adjusted difference, 0.5; 95% CI, 0.2 to 0.7; P < .001). From year 7 to 20, both groups had a mean annual 1.8 hospital days (adjusted difference, 0.0; 95% CI, -0.3 to 0.3; P = .95). Surgery patients had a mean annual 1.3 nonprimary care outpatient visits during the years 2 through 6 vs 1.1 among the controls (adjusted difference, 0.3; 95% CI, 0.1 to 0.4; P = .003), but from year 7, the 2 groups did not differ (1.8 vs 1.9 mean annual visits; adjusted difference, -0.2; 95% CI, -0.4 to 0.1; P = .12). From year 7 to 20, the surgery group incurred a mean annual drug cost of US $930; the control patients, $1123 (adjusted difference, -$228; 95% CI, -$335 to -$121; P < .001). CONCLUSIONS: Compared with controls, surgically treated patients used more inpatient and nonprimary outpatient care during the first 6-year period after undergoing bariatric surgery but not thereafter. Drug costs from years 7 through 20 were lower for surgery patients than for control patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01479452.

Lifetime productivity losses associated with obesity status in early adulthood: a population-based study of Swedish men.

BACKGROUND: Obesity is a well-known risk factor for sick leave, disability pension and premature death. Obesity is therefore presumably related to increased productivity losses. OBJECTIVE: The aim of this study was to estimate the lifetime productivity losses to society associated with obesity status. METHODS: This study was based on a 38-year follow-up of a nationwide cohort of 45 920 Swedish men performing mandatory military conscription tests at age 18.7 ± 0.5 years. Body mass index (BMI) based on measured height and weight at the time of military conscription tests was used to define underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)) and obesity (≥30.0 kg/m(2)). Data on sick leave, disability pension and premature death were retrieved from national registers. The calculations were adjusted for socioeconomic index, smoking and muscular strength. RESULTS: Using the human capital approach, the lifetime productivity losses were calculated as 55.6 (95% CI 50.7, 62.0) × €1000 and 55.6 (95% CI 50.9, 61.4) × €1000 for underweight and normal weight, respectively, and 72.6 (95% CI 66.3, 80.7) × €1000 and 95.4 (95% CI 89.0, 102.9) × €1000 for overweight and obesity, respectively. If using the friction cost method instead, the estimated productivity losses were reduced by about 80%. CONCLUSION: Obesity is associated with almost twice as high productivity losses to society as for normal weight over a lifetime. These costs are important to include in health economic analyses of obesity intervention programmes in order to ensure an effective allocation of resources from a societal perspective.